Screening for GARS Variants in A Cohort of Chinese Patients With Inherited Peripheral Neuropathy

Abstract Background CMT2D is a rare subtype of axonal CMT, caused by the mutation of glycyl-tRNA synthetase (GARS) gene which is also a disease-causing gene of distal spinal muscular atrophy type V (dSMA-V) or hereditary motor neuropathy 5A (HMN5A). There were only several case reports in China, and no epidemiological study of CMT2D/ HMN5A yet.Methods We recruited the patients of Chinese Han descent clinically diagnosed with inherited peripheral neuropathy (IPN) from the Department of Neurology at Chinese PLA General Hospital (Beijing, China) from December 20, 2012 to July 31, 2019. All patients underwent a detailed medical history, neurological examination, laboratory examination, electrophysiological studies, and genetic testing.Results A total of 206 unrelated patients underwent genetic analysis, and we found four mutations of GARS from four different families, including c.794C>T (p.S265F), c.374A>G (p.E125G), c.1000A>T (p.I334F) and c.781T>G (p.Y261D), the first three of them were considered pathogenic. As for the three pathogenic mutation carriers, one patient was diagnosed as CMT2D, two patients were diagnosed as HMN5A.Conclusion GARS mutation is a rare cause of inherited peripheral neuropathy and the phenotype tends to be CMT2D or HMN5A. There might be a relatively higher mutation frequency in Asian population compared with Caucasians. Combination of clinical phenotype, auxiliary tests and genetic evidence to assess the pathogenicity of genetic variants in patients suspected as IPN is of vital importance.

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Mutation Analysis of GARS and Genotype-Phenotype Correlation in CMT2D/HMN5A in Chinese Patients

10.21203/rs.3.rs-43866/v2 ◽

2020 ◽

Author(s):

Bo Sun ◽

Zhengqing He ◽

Yanran Li ◽

Hongfen Wang ◽

Fei Yang ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Muscular Atrophy ◽

Trna Synthetase ◽

Chinese Patients ◽

Motor Neuropathy ◽

Chinese Han ◽

Spinal Muscular Atrophy Type ◽

Detailed Medical History ◽

Hereditary Motor Neuropathy ◽

Type V

Abstract BackgroundCMT2D is a rare subtype of axonal CMT, caused by a variant of the glycyl-tRNA synthetase (GARS) gene which is also a disease-causing gene of distal spinal muscular atrophy type V (dSMA-V) or hereditary motor neuropathy 5A (HMN5A). There were only several cases reported in China, all lacking an epidemiological study of CMT2D/ HMN5A.Methods206 patients of Chinese Han descent, clinically diagnosed with inherited peripheral neuropathy (IPN), were recruited in this study from December 20, 2012 to July 31, 2019. All patients underwent a detailed medical history screening, a neurological examination, a laboratory examination, several electrophysiological studies, and genetic testing.ResultsA total of 206 unrelated patients underwent genetic analysis. Four variants of GARS from four different families were found, including c.794C > T (p.S265F), c.374A > G (p.E125G), c.1000A > T (p.I334F), and c.781T > G (p.Y261D), with the first three being considered pathogenic. For the three pathogenic variant carriers, one was diagnosed with CMT2D, while the two others were diagnosed with HMN5A.ConclusionGARS mutation is a rare outcome of inherited peripheral neuropathy and the phenotype tends to be CMT2D or HMN5A.

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Mania following antidepressant discontinuation in depression: two case reports

Australasian Psychiatry ◽

10.1177/1039856217732470 ◽

2017 ◽

Vol 25 (6) ◽

pp. 617-621 ◽

Cited By ~ 2

Author(s):

Cecilia Sze Nga Kwok ◽

Leslie Eng Choon Lim

Keyword(s):

Selective Serotonin Reuptake Inhibitors ◽

Tricyclic Antidepressants ◽

Standard Treatment ◽

Late Onset ◽

Case Reports ◽

Asian Population ◽

Unipolar Depression ◽

Chinese Patients ◽

Manic Symptoms ◽

History Of

Objective: Antidepressant-induced mania and an antidepressant discontinuation syndrome are well documented, whereas mania occurring after antidepressant cessation has been infrequently reported. Method: We describe antidepressant discontinuation-related mania in two Chinese patients, as well as a review of the literature on this phenomenon in unipolar depression. Results: A 72-year-old man and a 65-year-old woman had late-onset depression with vascular risk factors, but no personal or family history of mood disorders. Manic symptoms started after stopping escitalopram and venlafaxine during depressive relapse, and resolved with the initiation of olanzapine and valproate. In the literature, 29 episodes of antidepressant discontinuation-related mania were reported. Tricyclic antidepressants were most frequently implicated, followed by selective serotonin reuptake inhibitors. There was spontaneous resolution of manic symptoms in half of the cases. Conclusion: This is the first report of antidepressant discontinuation-related mania in an Asian population, in the setting of late-onset depression. This phenomenon is rare and is amenable to standard treatment.

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Glycyl tRNA Synthetase Mutations in Charcot-Marie-Tooth Disease Type 2D and Distal Spinal Muscular Atrophy Type V

The American Journal of Human Genetics ◽

10.1086/375039 ◽

2003 ◽

Vol 72 (5) ◽

pp. 1293-1299 ◽

Cited By ~ 357

Author(s):

Anthony Antonellis ◽

Rachel E. Ellsworth ◽

Nyamkhishig Sambuughin ◽

Imke Puls ◽

Annette Abel ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Muscular Atrophy ◽

Trna Synthetase ◽

Disease Type ◽

Charcot Marie Tooth ◽

Spinal Muscular Atrophy Type ◽

Charcot Marie Tooth Disease ◽

Type V ◽

Tooth Disease

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Glycyl tRNA Synthetase (GARS) Gene Variant Causes Distal Hereditary Motor Neuropathy V

Case Reports in Pediatrics ◽

10.1155/2018/8516285 ◽

2018 ◽

Vol 2018 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

Peter Chung ◽

Hope Northrup ◽

Misbah Azmath ◽

Ricardo A. Mosquera ◽

Shade Moody ◽

...

Keyword(s):

Muscular Atrophy ◽

Trna Synthetase ◽

Motor Neuropathy ◽

Inherited Disorders ◽

Causative Gene ◽

Hereditary Motor ◽

Pathogenic Variants ◽

Neurogenic Muscular Atrophy ◽

Hereditary Motor Neuropathy ◽

Type V

Distal hereditary motor neuropathies (dHMN) are a rare heterogeneous group of inherited disorders specifically affecting the motor axons, leading to distal limb neurogenic muscular atrophy. The GARS gene has been identified as a causative gene responsible for clinical features of dHMN type V in families from different ethnic origins and backgrounds. We present the first cohort of family members of Nigerian descent with a novel heterozygous p.L272R variant on the GARS gene. We postulate that this variant is the cause of dHMN-V in this family, leading to variable phenotypical expressions that are earlier than reported in previous cases. The exact cause for the observed clinical heterogeneity within the family is unknown. One explanation is that there are modifier genes that affect the phenotype. These cases highlight the possibility of considering pathogenic variants in the GARS gene as a potential cause of early onset axonal polyneuropathy with atypical presentation.

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